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Gastroenterology. 2014 Mar;146(3):669-680.e2. doi: 10.1053/j.gastro.2013.11.044. Epub 2013 Dec 4.

Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass.

Author information

1
Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address: salehim@uc.edu.
2
Cardiometabolic Risk Unit, CNR Institute of Clinical Physiology, Pisa, Italy.
3
Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio; Cincinnati VA Medical Center, Cincinnati, Ohio.

Abstract

BACKGROUND & AIMS:

Postprandial glycemia excursions increase after gastric bypass surgery; this effect is even greater among patients with recurrent hypoglycemia. These patients also have increased postprandial levels of insulin and glucagon-like peptide 1 (GLP-1). We performed a clinical trial to determine the role of GLP-1 in postprandial glycemia in patients with hyperinsulinemic hypoglycemia syndrome after gastric bypass.

METHODS:

Nine patients with recurrent hypoglycemia after gastric bypass (H-GB), 7 patients who were asymptomatic after gastric bypass (A-GB), and 8 healthy control subjects underwent a mixed-meal tolerance test (350 kcal) using a dual glucose tracer method on 2 separate days. On 1 day they received continuous infusion of the GLP-1 receptor antagonist exendin (9-39) (Ex-9), and on the other day they received a saline control. Glucose kinetics and islet and gut hormone responses were measured before and after the meal.

RESULTS:

Infusion of Ex-9 corrected hypoglycemia in all patients with H-GB. The reduction in postprandial insulin secretion by Ex-9 was greater in the H-GB group than in the other groups (H-GB, 50% ± 8%; A-GB, 13% ± 10%; controls, 14% ± 10%) (P < .05). The meal-derived glucose appearance was significantly greater in subjects who had undergone gastric bypass compared to the controls and in the H-GB group compared to the A-GB group. Ex-9 shortened the time to reach peak meal-derived glucose appearance in all groups without a significant effect on overall glucose flux. Postprandial glucagon levels were higher among patients who had undergone gastric bypass than controls and increased with administration of Ex-9.

CONCLUSIONS:

Hypoglycemia after gastric bypass can be corrected by administration of a GLP-1 receptor antagonist, which might be used to treat this disorder. These findings are consistent with reports that increased GLP-1 activity contributes to hypoglycemia after gastric bypass. ClinicalTrials.gov, Number: NCT01803451.

KEYWORDS:

Glucagon-like Peptide 1; Hyperinsulinemic Hypoglycemia Syndrome; Islet Function; Roux-en-Y Gastric Bypass Surgery

PMID:
24315990
PMCID:
PMC3943944
DOI:
10.1053/j.gastro.2013.11.044
[Indexed for MEDLINE]
Free PMC Article

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